Saso Srdjan, Petts Gemma, Chatterjee Jayanta, Thum Meen-Yau, David Anna L, Corless David, Boyd Michael, Noakes David, Lindsay Iain, Del Priore Giuseppe, Ghaem-Maghami Sadaf, Smith J Richard
Clinical Research, Division of Surgery and Cancer, Institute of Reproductive & Developmental Biology, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
Department of Pathology, Imperial College Healthcare NHS Trust, St Mary's Hospital, Praed Street, London W2 1NY, UK.
Eur J Obstet Gynecol Reprod Biol. 2014 Nov;182:185-93. doi: 10.1016/j.ejogrb.2014.09.029. Epub 2014 Sep 28.
Uterine transplantation (UTx) has been proposed as a treatment option for women diagnosed with absolute uterine factor infertility. Allogeneic UTx has been attempted in a number of animal models, but achieving an adequate blood supply for the transplanted uterus still presents the biggest challenge. Microvascular re-anastomosis was unsuccessful in a number of animal models. The aim was to assess whether a large vessel aortic-caval vascular patch technique can bring about long-term graft survival after allogeneic UTx in a rabbit model.
A longitudinal study involving uterine cross transplantations (n=9 donors, n=9 recipients) was performed in New Zealand white rabbits using an aortic-caval macrovascular patch harvested as part of the uterine allograft. All rabbits were allogeneic and of proven fertility, with at least one previous litter each. The end result of the donor graft harvest was a total hysterectomy transecting across the vagina and the most lateral aspects of the uterine horns together with an aortic-caval macrovascular patch (aorta, inferior vena cava, common and internal iliacs, and uterine arterial and venous tree). Tacrolimus (500 μg twice daily) was administered for immunosuppression post-transplant. The recipients were closely monitored until death or euthanasia.
In this case series, long-term rabbit survival was 11% (n=1). Surgical survival was 56% (n=5). Three rabbits (UTx #3, #4 and #8) died intra-operatively as a result of blood aspiration, ventricular hematoma, and massive hemorrhage. Three does (#1, #2, #7 and #9) died within the first 24 h as a result of the veno-vena and anastomosis breakdown. Does #6 and #9 died secondary to pre-operative pneumonia and a pulmonary embolus, respectively. Only one rabbit survived longer than a month.
Our method used a macrovascular patch technique to ensure adequate blood supply to the donor uterine graft. We have demonstrated the feasibility of uterine allotransplantation using this technique in the rabbit, but were unable to demonstrate a higher long-term survival percentage because of issues related to using a rabbit model.
子宫移植(UTx)已被提议作为诊断为绝对子宫因素不孕女性的一种治疗选择。同种异体子宫移植已在多种动物模型中尝试,但为移植子宫提供充足的血液供应仍然是最大的挑战。在一些动物模型中,微血管重新吻合术未成功。目的是评估在兔模型中,大血管主动脉 - 腔静脉血管补片技术能否在同种异体子宫移植后实现长期移植物存活。
在新西兰白兔中进行了一项纵向研究,涉及子宫交叉移植(9只供体,9只受体),使用作为子宫同种异体移植物一部分收获的主动脉 - 腔静脉大血管补片。所有兔子均为同种异体且生育能力已得到证实,每只至少有过一窝仔。供体移植物收获的最终结果是全子宫切除术,横断阴道和子宫角最外侧部分,连同主动脉 - 腔静脉大血管补片(主动脉、下腔静脉、髂总动脉和髂内动脉以及子宫动静脉树)。移植后给予他克莫司(每日两次,每次500μg)进行免疫抑制。密切监测受体直至死亡或安乐死。
在这个病例系列中,兔子的长期存活率为11%(n = 1)。手术存活率为56%(n = 5)。3只兔子(UTx #3、#4和#8)在术中因血液抽吸、心室血肿和大量出血死亡。3只母兔(#1、#2、#7和#9)在术后24小时内由于静脉 - 静脉吻合破裂死亡。#6和#9号母兔分别因术前肺炎和肺栓塞继发死亡。只有1只兔子存活超过1个月。
我们的方法采用大血管补片技术以确保对供体子宫移植物有充足的血液供应。我们已经证明了在兔中使用这种技术进行子宫同种异体移植的可行性,但由于使用兔模型相关的问题,未能证明更高的长期存活率。